Note: Descriptions are shown in the official language in which they were submitted.
W~92/10458 PCT/US911~725~
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MANUFACTURE OF 2,6-HYDROXYNAPHTHOIC ACID
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Technical Field
This inventio~ relates to the production
of 2,6~hydroxynaphthoic acid (2,6-~NA) beginning
with 2-naphthol. In particula~, it relates to the
use of cesium or r--bidium to replace the hydroxyl
proton of the 2-naphthol and then reacting the
cesium or rubidium naphthoxide with carbon dioxide
in the presence of cesium or rubidium carbonate.
Preferred conditions include recommended solvents
and pressure ranges.
Background of the Invention
Prior to the present invention it has been
known to convert 2-naphthol to 2,3-hydroxynaphthoic
acid (2,3-HNA~ by reacting the 2-naphthol with
sodium hydroxide and then carboxylating the
resulting sodium naphthoxide with carbon dioxide.
It has also been known that the carboxylation tends
to shift to the 6-position if potassium is used
instead of ~odium. Temperatures also appear to
affect the formation of 2,6-HNA as opposed to
2,3-HNA.
After carboxylation, the proton at the
carboxylation site is lost and is picked up by a
second 2-naphthoxide molecule. Thus, for every mole
of product formed, a mole of starting ~aterial is
formed. This means the best possible conversion is
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WO92/10458 PCT/~S91t~7250
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50%. ~ddition of potassium carbonate during the
second step improves conversion. The products
2,6-HNA, 2,3-HNA and 2-naphthol can be separated by
modifying the pH of an aqueous solution containing
the three. Typically, 2,6-~NA can be isolated in
thi~ manner with 97-99% purity, with 2,3-HNA being
the major impurity. It is important to adju~t pH
precisely and accurately as this can affect the
yield and purity of the desired product.
The patent literature contains two
processes for the carboxylation of potassium
2-naphthoxide. In one process, a flow of carbon
dioxide is passed continuously through the apparatus
during carboxylation, claiming a higher yield than
in the process without continuous CO2 flow.
Summary of the Invention
We have found that surprisingly improved
results toward, particularly, conversion to 2~6-HNA
are achieved in a cesium or rubidium system as
compared to a potassium system. Our process for the
manufac~ure of 2,6-HNA involves ~he reactivn of
2-naphthol with cesium or rubidium hydroxide to form
ce~ium or rubidium naph~hoxide, and reacting the
cesium or rubidium naphthoxide with carbon dioxide
in the pre~ence of cesium or rubidium carbonate, at
a temperature of about 220 to about 300C, a
pressure of about 20 to about l00 psig, and in a
solvent (carrier) medium of a high boiling
hydrocarbon0 i.e. a linear or cyclic hydrocarbon
having about l0 to about 25 carbon atoms.
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Detailed Description of the Invention
We have found that a dramatic increase in
t yield of 2,6-HNA can be obtained with.our process as
compared to processes of the prior art.
Selectivities. in particular are considerably
improved as compared to.analogous potassium
reactions which our investigations indicated were
representative of the best prior artO
Our invention comprises a three-step
process:
(1) 2-naphthol is neutralized with cesium
or rubidium hydroxide;
(2) the resulting cesium or ru~idium
naphthoxicie product is dried by any convenient
method; and
(3) the cesium or rubidium naphthoxide is
reacted with carbon dioxide in the presence of about
5 to about 60% cesium or rubidium carbonate at
temperatures in the range about 220 to about 300C
and pressures about 20 to about 100 psig in a
suitable carrier, for a period of about 4 to about
10 hours.
Our invention is illustrated and compared
to the prior art in the examples below.
Table I presents results using certain
variations of the prior art potassium method.
Example B may be taken as representative. Following
is a detailed description of example 8:
In a 300 ml autoclave was placed
2-naphthol (36.04 g, 250 mmol~, 87O0% potassium
hydroxide (16013 g, 250 mmol~, potassium car~onate
(17.28 g, 125 mmol), 15 ml water, and 100 ml
tetradecane. The mixture was stirred at room
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temperature under a slow purge of argon for 1 hour
before heating to 250C and holding at that
temperature for 3 hours, at which-time ca. 21 ml
water and 5 ml tetradecane had been collected in a
knock-Gut pot. After heating to 265C, the
autoclave was charged with 45 psi carbon dioxide
with a flow of 250 ml per minute.
Conditions were maintained for 6 hours before
depressurizing and cooling to room temperature. The
contents of the autoclave were transferred to an
erlenmeyer flask and wa~er added until a total
volume of ca. 550 ml existed. The reaction mixture
was heated at 80-90C for 30 minutes and the organic
layer containing 2-naphthol removed. The aqueous
layer was acidified to pH 7.0 via addition of 1 M
H2504 and extracted twice with 350 ml toluene at
80C. The agueous phase was cooled to room
temperature and further acidified to pH 4.0 by
addition of 1 M H2SO4, at which time the 2,6-HNA
precipitate was collected by filtration, washed with
water and dried. There was isolated 11.~4 g (25~)
of a tan solid which was 97.6% 2,6-HNA, 2.4% 2,3-HNA
by G. C. analysis of the material after silylation
with N,N-bis(trimethylsilyl~acetamide. The melting
point was about 240-248C. Fur~her acidification of
the filtrate to pH 2.0 with 1 M ~SO4 gave 1.4 9
(3%) of a yellow solid which was B6.3%, 2,3-~N~,
13.7% 2,6-HNA by G. C. analysis. The combined
organic phases were extracted with 5% NaOH (3 X 100
ml) and the combined aqueous extracts acidified to a
pH less than 2 by addition of 3 M ~Cl. Filtration,
a water wash, and drying gave 21.90 g (61%) of
recovered 2-naphthol.
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Variations from the example ~ procedure,
such as the amount of potassium carbonate, the
solvent, time of reaction and pressure, are shown in
Table I.
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: Table I
2,6-~NA Production Using Potassium Cation (Prior Art)
Selectivity
Special Con~er- ~2,6-HNA~
ND. Conditions Solvent Time Temp Press sion 2?3-71MA~
1. 10~ K2CO3 IPN1 6 h 260C 42 PSi 46X 37%, 13
2- 50Z K2CO3 IPN1 6 h 265C 45 psi 38~ 58~, 13%
3. 10% K2CO3 IPN1 8 h 265C 45 psi 39Z 56%7 18%
4~ 50X K2C03 Kero- 6 h 265C 45 PSi 28% 57%, 14
sene
5. 50% K2C03 Keene~6 h 265C 45 psi 32% 56X, 12X
6. 10~ K2C03 Kero- 6 h 265C 55 psi 42% 40Z, 12X
sene
7. 10% K2C03 TMPI2 6 h 265C 60-75 45% 44Z, 27%
8. 50% K2CO3 Tetra- 6 h 265~C 45 psi 39Z 64~, 8
decane
9. 10% K2C03 Tetra-22 h 265C 45 PSi 51% 53%4, 4
decane
10. 10% K2C03 Te~ra- 8 h 265C 55 psi 45% 58%5 9
decane
11. 10X K2C03 Hexa 8 h 265C 65 psi 40Z 50%6, 12X
decane
Isopropylnaphthalene
Trimethylphenylindane
~7. 6Z pure
498.1% pure
597.6X pure
i 696.2X pure
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Results of the following examples 12-18
illu~trate the improvements obtained by using th~
cesium or rubidium of our invention, and are ~hown
in Table II. :
_sium Method (Table II, example 12)
Using 2-naphthol (36.04 g, 250 mmol),
74.96 g of 50 wt~ a~ueous cesium hydroxide (250
mmol), cesium carbonate (B.14 9, 25 mmol) and 95 ml
hexadecane gave 16.72 g (36%) 2,6-~NA
(G. C. analysis 98.5~ 2,6-HNA, 1.5% 2,3-HNA), 1.30 g
(4~) 2,3- HNA (G. C. analysis 95.5% 2,3 -HNA, 4.5%
2,6-HNA) and 19.09 g (53%) recovered 2-naphthol.
Cesium Method (Table II,_example 13
Vsing 2-naphthol (36.04 g, 250 mmol),
74.96 g of 50 wt~ aqueous cesium hydroxide (250
mmol), cesium car`oonate (B.14 g, 25 mmol) and 95 ml
hexadecane gave 17.53 g (37%) 2,6-HN~
(G. C. analysis 98.0% 2,6-HNA, 2.0~ 2,3-HNA), l.90 g
(4%) 2,3-HNA (G. C. analysis 88.1~, 2,3 HNA, 11.9%
2,6-HNA) and 16.51 g (46%) recovered 2-naphthol.
Cesium Method (Table II, example 14)
Using 2 naphthol (36.04 g, 250 ~mol),
74.96 g of 50 wt% aqueous cesium hydroxide (250
mmol), cesium carbonate (8.14 g, 25 ~mol), 95 ml
hexadecane and a carbon dioxide pressure of 55 psi
gave 1~.27 g (35%) 2,6-HNA, 1.84 g (4%) 2,3-HNA,
both having a similar purity as above and 19.46 g
(54~) recovered 2-naphthol.
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Cesium Method (Table II, example 15)
using 2-naphthol-~36.04 9, 250 mmol),
74.96 g of 50 wt% aqueous cesium hydroxide (250
mmol), cesium carbonate (8.14 g, 25 mmol), 95 ml
hexadecane and a carbon dioxide pressure of 85 psi
gave 18.21 g (39%) 2,6-HNA (G. C. analy~is 98.8%
2,6-HNA, 1.2% 2,3-HNA), 3.59 g (8%) 2,3-HNA (G. C.
analysis 78 . 0% 2,3-HNA, 12.0% 2,6-HNA) and 15.73 g
(44%) recovered 2~naphthol.
Cesium Method Excluding Cesium
Carbonate (Table II, exa~ple 16)
Processing 2-naphthol (36.04 g, 250 mmol),
74.g6 g of 50 wt% aqueous cesium hydroxide (250
mmol), and 95 ml hexade~ane yielded 11. 23 g (24%)
2,6-HNA (G. C. analysis 97.4% 2,6-HNA, 2.6%
2,3-HNA), 2.07 9 (4%) 2,3-~NA (G. C. analysis 87.5~
2,3-HNA, 12.5% 2,6-HNA~ and 23.10 9 (64%) recovered
2-naphthol.
Mixture 90% Potassium and 10% Cesium
(Table II, example 17)_
With 2-naphthol (36.04 g, 250 mmol), 7.50
g of 50 wt~ aqueous cesium hydroxide (25 mmol),
87.9% potassium hydroxide (14.02 g, 225 mmol),
potassium carbonate (3.46 9, 25 mmol), 15 ml wa~er,
and 95 ml hexadecane, the usual reaction produced
10.66 g (23%) 2,6-HNA (G. C. analysis 96.6% 2,6-HNA,
3.4% 2,3~HNA), 3.00 g (6%) 2,3-HNA (G. C. analysis
84.6%, 2,3-HNA, 15.4% 2,6-HNA) and 19.13 g (53%)
recovered 2-naphthol.
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Rubidium Method tTable II, example 18)
using 2-naphthol (36.04 g, 250 mmol),
51.24 g of 50 wt% aqueous rubidium hydroxide
(250 mmol), rubidium carbonate (5.77 g, 25 mmol) and
95 ml hexadecane, there was obtained 16.53 g ~35%)
2,6-HN~, 1.82 g (4~) 2,3-HNA, both having a ~imilar
purity as above and 20.98 g (58~) recovered
2-naphthol .
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Table II
2,6-HNA Production Using Cesiuml or Rubidium Cation2
Selec~ivity
Special j : . Conver- (2,6-HNA,
No Conditions Solvent Time Temp Press sion 2,3-~NA)
12. lOX Hexa- 6 h 265C 4S psi 47% 76%3, 8
CS2C3 decane
13. lOX Hexa- 6 h 265C 45 psi 54~ 68%4, 7X
CS2C3 decane
14. 10% Hexa- 6 h 265C 55 psi 46% 76%, 9%
CS2C3 decane
15. 10% Hexa- 6 h 265C ~35 psi 56~ 70%, 14
CS2C3 decane
16. no Hexa- 6 h 265C 45 psi 36% 67~, llX
Cs2C03 decane
17. 90% K+, Hexa- 6 h 265C 45 psi 47~ 49~, 13
10% Cs+ decane
18. 10% ~exa- 6 h 265C 45 psi 42% 83Z, lOX
Rb2C3 decane
Examples 12-17.
Example 18.
98.~ pur~
98.0X pure
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As can be seen, the 2,6-HNA selectivity
was much improved with cesium over the analogous
potassium reaction, accompanied by a ~mall increase
in conversion ~compare Table I, example 8 with Table
II, example 12). The result was an approximate 44%
increase in isolated yield of 2,6-HNA.
A few variables were tested with the
cesium examples. First, an increase in carbon
dioxide pressure to 85 psi doubled 2,3-HNA
selectivity (compare example 15 with examples 12 and
13). Next, a reaction excluding cesium carbonate
gave conversion and selectivity numbers similar to
the potassium reactions. The presence of cesium or
rubidium carbonate appears to be essential ~in the
range of about 5% to about 60% of the naphthol salt)
for maximized conversion and selectivity. The
possibility that only a small amount of cesium would
give increased conversion and selectivity was
dispelled in example 17. As can be seen in example
lB, an increase in conversion and the best
selectivity was found with rubidium.
